摘要Objective Glioma is a highly lethal tumor of the central nervous system(CNS)with limited therapeutic options.Recent evidence has highlighted the role of dysregulated alternative splicing in glioma progression.Although OY-TES-1 has been proposed as a potential therapeutic target,its splice isoforms have not been fully characterized.This study aimed to identify the clinically relevant splice variant of OY-TES-1 associated with glioma progression and to evaluate its potential as a target for innovative therapeutic strategies against this challenging disease.Method The potential splicing patterns of OY-TES-1,along with their relative frequency and correlation with patient sur-vival,were analyzed via the TCGA SpliceSeq and OncoSplicing databases.RNA-Seq by expectation maximization(RSEM)values and clinicopathological data for all OY-TES-1 gene transcripts were downloaded from the UCSC Xena database,and Cox regression analysis was performed for both univariate and multivariate prognostic assessments.The expression of OY-TES-1 mRNA in glioma and normal brain tissues was detected via RT-PCR.The relationships between OY-TES-1 mRNA expression and the clinicopathological characteristics of glioma patients were analyzed via the x2 test.OY-TES-1-V5a was overexpressed in glioma cells through transient transfection with plasmids as well as stable transfection with lentivirus for further functional analysis.Glioma cell proliferation was assessed via the Cell Counting Kit-8(CCK-8)assay.Migration and invasion abilities were evaluated via wound healing,Transwell,and Transwell Matrigel assays.Apoptosis was analyzed by flow cytometry.Results Bioinformatic analysis revealed four alternative splice variants of OY-TES-1 in glioma,among which OY-TES-1-V5a presented a relatively high percent spliced-in(PSI)value that was associated with significantly shorter overall survival.OY-TES-1-V5a was further identified as an independent prognostic risk factor for glioma patients,as its mRNA expression was significantly associated with Karnofsky performance status(KPS),tumor grade,and isocitrate dehydrogenase 1(IDH1)mutation status.RT-PCR validation confirmed that OY-TES-1-V5a was overexpressed in glioma tissues compared with normal brain tissues.Functionally,forced expression of OY-TES-1-V5a enhanced glioma cell proliferation,migration,and invasion while suppressing apoptosis.Conclusions The OY-TES-1 splice variant V5a is highly expressed in glioma,is associated with poor prognosis,and actively drives malignant behavior,indicating its potential utility as a prognostic biomarker and a candidate target for therapeutic intervention.